The Neuropathology Core has both provided a service to the projects and has also made significant contributions to understanding the etiology and pathogenesis of prion diseases. With regard to the latter, the routine examination of tissue sections has in itself been hypothesis generating. The Aims of the Neuropathology Core are: (1) To sacrifice animals, remove organs, and prepare them for neurohistological and immunohistochemical staining and for histoblotting; (2) to localize PrPSc in aldehyde fixed tissue sections pretreated by the hydrolytic autoclaving technique and on histoblots; (3) to prepare snap frozen skeletal muscle samples for enzyme histochemical evaluation in selected animals; (4) to fix peripheral nerve in glutaraldehyde, embed in araldite plastic and prepare toluidine blue stained sections in selected animals; (5) to quantify the degree of spongiform degeneration, reactive astrocytic gliosis and PrPSc accumulation; (6) to maintain a data base for retrieval of the several thousand animals which have been processed in part by the Neuropathology Core of this Program Project as well as by other Neuropathology Cores which have been part of other prion disease program projects; and (7) to consult with and prepare photomicrographs and data graphs to project investigators for publication.